Our work addresses a novel biocompatible plasmon-enhanced nanostructure approach based on the combination of metal nanoparticles, light emitting polymer-based nanostructures, and scalable cellulose nanofiber templates via a one-step facile electrospinning process that can easily be applied to biomedical devices. In collaboration with the Team of Prof. Lee Goldstein in the Boston University medical campus, we demonstrated light emission from small-size (below 200nm) polymer nanoparticles coupled to plasmonic nanoparticles and to light-emitting biocompatible molecules. In order to fully demonstrate the potential of our novel plasmonic nanostructures we developed Magnetic resonance imaging (MRI) reagent doped Polycaprolactone (Core)-Polyethylene glycol (shell) core-shell nanoparticles and studied their size distribution and dispersion properties in a phosphate buffered saline solution. Our materials were optimized in order to obtain no aggregation of the nanoparticles in solution. The presence of MRI reagent in nanoparticles were demonstrated via Inversion Recovery Sequences (IR) by characterizing the different T1 relaxation times. The concentration of Gd in the nanoparticles dispersion was estimated with different dilution of Gd commercial reagent as a reference. In addition, we combined facile electrospinning fabrication with top down nano-deposition and demonstrated a novel and scalable plasmonic resonant medium for rapid and reliable Raman scattering sensing of molecular monolayers and bacteria. Specifically, aided by PCA multivariate data analysis techniques, we demonstrated fingerprinting Surface Enhanced Raman Scattering (SERS) spectra of different bacteria strains (E. Coli K12, E. coli BL21 (DE3) and E. coli DH 5α) entrapped in our novel plasmonic networks. Finally, in this thesis we have also addressed the development of novel, Si-compatible and largely tunable plasmonic materials for biosensing applications in the mid-infrared spectral range and developed a novel type of transparent conductive oxide based on the Indium Silicon Oxide (ISO) material (Indium Silicon Oxide) that features enhanced surface smoothness and thermal stability compared to Indium tin oxide (ITO) and Titanium nitride (TiN) alternative plasmonic materials. In collaboration with our collaborators at Columbia University, we demonstrated the tunability of near-field plasmonic resonances from 1.8 to 5.0 μm as a function of different annealing temperature. This work provides an enabling first-step towards the development of novel Si-compatible materials with tunable plasmon resonances for metamaterials and sensing devices that operate across the infrared spectrum. / 2019-07-02T00:00:00Z

Dans le cadre de cette thèse intitulée “Synthèse et caractérisation de nanoparticules à base de silicium pour des applications de diagnostique”, nous avons conçu des nanosondes basées sur des systèmes de petites nanoparticules à base de silicium (<5 nm) (NPs) portant différentes molécules fonctionnelles sur leur surface. Les NPs de Si ont été synthétisées, caractérisées et fonctionnalisées pour une utilisation dans les applications d'imagerie in vivo et d'électrochimiluminescence (ECL). Pour l’imagerie, une sonde active de tomographie par émission de positrons (TEP) et un colorant émissif ont été utilisés pour montrer les capacités d’imagerie et l’élimination rapide des NP de Si des corps des souris. La fixation d'un sucre sur les NPs de Si a été utilisée pour étudier le passage à travers la barrière hémato-encéphalique (BHE). Enfin, la fixation de complexes de ruthénium et d'iridium a montré que les NP de Si possédaient une bonne efficacité en tant que sondes dans les applications ECL. / Within the work of this thesis, entitled “Synthesis and characterisation of silicon based nanoparticles for diagnostic applications”, we have designed nanobrobes based on systems of small (< 5 nm) silicon-based nanoparticles (Si NPs) bearing different functional molecules on the surface. Si NPs were synthesised, thoroughlycharacterised and functionalised for use in in vivo imaging and electrochemiluminescence (ECL) applications. For imaging, a positron emission tomography (PET) active probe and an emissive dye have been used to show the effective imaging capabilities and fast clearance of the Si NPs from the bodies of mice.Attachment of a sugar to the Si NPs has been used to study passage through the blood-brain-barrier (BBB). Finally, attachment of ruthenium and iridium complexes has shown that the Si NPs possess some good efficiency as probes in ECL applications.

Two-photon absorption and upconverted fluorescence has been utilized in a variety of applications in pure science and engineering. Multiphoton-based techniques were used in this research in order to understand photophysical and chemical characteristics of several fluorescent dyes and to demonstrate some of their key applications. Two-photon fluorescence microscopy (2PFM) has become a powerful technique in bio-photonics for non-invasive imaging in the near-infrared (NIR) region (700~1000 nm) that often results in less photobleaching. In Chapter 1, there is a brief introduction to fluorescence, examples of fluorescence materials, and a discussion of the advantages of two-photon absorption. 2PFM imaging was utilized in Chapters 2 to 4 for various applications. In Chapter 2, a new squaraine dye is introduced and its linear and nonlinear photophysical properties are characterized. This compound has very high two-photon absorption (2PA) cross sections and high photostability both in an organic solvent and when encapsulated in micelles. Based on these properties, this dye was demonstrated as a near-infrared (NIR) probe in in vitro 2PFM imaging with excitation over 800 nm wavelength. In Chapter 3, new profluorescent nitroxides are introduced. Nitroxide radicals are utilized for electron paramagnetic resonance (EPR) spectroscopy and in biological systems as some are known, in some manner, to mimic the behavior of superoxide dismutase (SOD) that detoxifies or mitigates oxidative stress by trapping free radicals. Here, two profluorescent nitroxides investigated for use as a two-photon fluorescent oxidative stress indicator in in vitro two-photon fluorescence microscopy (2PFM) imaging. In Chapter 4, two-photon excited (2PE) fluorescence of a conjugated polyelectrolyte (CPE), PPESO3, was studied in methanol and in water. The results of CPE quenching studies were comparable under both one-photon excitation conditions and two-photon excitation. CPE coated silica nanoparticles were incubated in HeLa cells and 2PFM imaging was demonstrated for this new class of fluorescent probe. Supramolecular structures based on organized assemblies/aggregation of chromophores have attracted widespread interest as molecular devices with potential applications in molecular electronics, artificial light harvesting, and pharmacology. In Chapter 5, J-aggregate formation was investigated for two porphyrin-based dyes, 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin (TPPS, 4) and an amino tris-sulfonate analog (5) in water via UV-vis, fluorescence, and lifetime decay studies. The effect of aggregation on two-photon absorption properties was also investigated. A functionalized norbornene-based homopolymer, synthesized by the ring opening metathesis polymerization technique was used as a J-aggregation enhancement template and had a role of polymer-templating to facilitate porphyrin aggregation and modulate 2PA. In Chapter 6, squaraine dye aggregates templated with single wall carbon nanotubes (SWCNTs) that were atomically clean were studied by using optical absorption spectroscopy, atomic force microscopy (AFM), and photoconductivity measurements. SWCNTs selectively promote the formation of squaraine dye aggregates with a head-to-head stacking arrangement, and these dye aggregates effectively photosensitize SWCNTs, demonstrating that this novel approach can yield highly photosensitized devices.

Recent, cooperative advances in chemistry, biology, computing, photophysics, optics, and microelectronics have resulted in extraordinary developments in the biological sciences, resulting in the emergence of a novel area termed 'biophotonics'. The integrative and interdisciplinary nature of biophotonics cuts across virtually all disciplines, extending the frontiers of basic cellular, molecular, and biology research through the clinical and pharmaceutical industries. This holds true for the development and application of the novel imaging modality utilizing multiphoton absorption and its extraordinary contribution to recent advances in bioimaging. Intimately involved in the revolution of nonlinear bioimaging has been the development of optical probes for probing biological function and activity. The focus of this dissertation is in the area of probe development, particularly conjugated organic probes, optimized for efficient two-photon absorption followed by upconverted fluorescence for nonlinear, multiphoton bioimaging applications. Specifically, [pi]-conjugated fluorene molecules, with enhanced two-photon absorbing (2PA) properties and high photostability, were prepared and characterized. Contemporary synthetic methods were utilized to prepare target fluorene derivatives expected to be highly fluorescent for fluorescence imaging, and, in particular, exhibit high two-photon absorptivity suitable for two-photon excitation (2PE) fluorescence microscopy. The flexibility afforded through synthetic manipulation to integrate hydrophilic moieties into the fluorophore architecture to enhance compatibility with aqueous systems, more native to biological samples, was attempted. Incorporation of functional groups for direct covalent attachment onto target biomolecules was also pursued to prepare fluorene derivatives as efficient 2PA reactive probes. Linear and two-photon spectroscopic characterizations on these novel compounds reveal they exhibit high 2PA cross-sections on the order of ~100 GM units, nearly an order of magnitude greater than typical, commonly used fluorophores utilized in nonlinear, multiphoton microscopy imaging of biological samples. Photostability studies of representative fluorene derivatives investigated and quantified indicate these derivatives are photostable under one- and two-photon excitation conditions, with photodecomposition quantum yields on the order of 10[super-5]. Preliminary cytotoxicity studies indicate these fluorene derivatives exhibit minimal cytotoxic effects on proliferating cells. Finally, their ultimate utility as high-performance, 2PA fluorescent probes in 2PE fluorescence microscopy imaging of biological samples was demonstrated in both fixed and live cells. Due to the low cytotoxicity, high photostability, efficient 2PA, and high fluorescence quantum yield, the probes were found suitable for relatively long-term, two-photon fluorescence imaging of live cells, representing a significant advance in biophotonics.

Fluorescence spectroscopy has been considered to be one of the most important research techniques in modern analytical chemistry, biochemistry, and biophysics. At present, fluorescence is a dominant methodology widely used in a great number of research domains, including biotechnology, medical diagnostics, genetic analysis, DNA sequencing, flow cytometry, and forensic analysis, to name just a few. In the past decade, with the rapid development of fluorescence microscopy, there has been a considerable growth in applying fluorescence technique to cellular imaging. The distinguished merits of fluorescence techniques, such as high sensitivity, non-invasiveness, low cytotoxicity, low cost, and convenience, make it a promising tool to replace radioactive tracers for most biochemical measurements, avoiding the high expense and difficulties of handling radioactive tracers. Among the wide range of applications of fluorescence technique, fluorescent sensing of various cations and anions is one of the most important and active areas. This dissertation is all about developing fluorescent sensors for physiologically significant ions, including F-, K+, Fe3+, and Ca2+. All of these sensors demonstrate fluorescence "turn-on" response upon interacting with their respective ions, which makes them much more appealing than those based on fluorescence quenching mechanisms. In Chapter II, a novel highly selective fluorescence turn-on F- sensor (FS), comprised of a fluorene platform serving as the chromophore, and two 1,2,3-triazolium groups functioning as the signaling moieties, is described. The function of FS is established on the basis of deprotonation of the C-H bonds of 1,2,3-triazolium groups, which makes FS the first reported anion sensor based on the deprotonation of a C-H bond. Easy-to-prepare test strips were prepared for determining F- in aqueous media, providing an inexpensive and convenient approach to estimate whether the concentration of F- contained in drinking water is at a safe level. Chapter III contains an optimized synthesis of a reported K+-selective group (TAC), and the development of two TAC-based fluorescence turn-on K+ sensors (KS1 and KS2). The synthetic route of TAC is shortened and its overall yield is enhanced from 3.6% to 19.5%. Both KS1 and KS2 exhibited excellent selectivity toward K+ over other physiological metal cations, high sensitivity for K+ sensing, and pH insensitivity in the physiological pH range. Confocal fluorescence microscopy experiments demonstrate that they are capable of sensing K+ within living cells. 2PA determination reveals that KS2 has a desirable 2PA cross section of 500 GM at 940 nm, which makes it a two-photon red-emitting fluorescent sensor for K+. Chapter IV describes the development of a novel BODIPY-based fluorescence turn-on Fe3+ sensor (FeS). FeS is a conjugate of two moieties, a BODIPY platform serving as the fluorophore and a 1,10-diaza-18-crown-6 based cryptand acting as the Fe3+ recognition moiety. FeS displays good selectivity, high sensitivity, reversibility, and pH insensitivity toward Fe3+ sensing. Based on its excellent performance in determining Fe3+ and very low cytotoxicity, FeS was effectively applied to sensing Fe3+ in living cells. In Chapter V, a new BODIPY-based fluorescence turn-on sensor (CaS) was designed and synthesized for selectively and sensitively determining Ca2+. CaS is comprised of two moieties, a BODIPY fluorophore and a Ca2+ complexing unit. CaS demonstrated selective fluorescence turn-on response towards Ca2+ over other biological metal cations. Moreover, CaS exhibited desirable sensitivity for Ca2+ detection, which makes it more suitable for extracellular Ca2+ determination. In addition, CaS was insensitive to the pH of the physiological environment, especially in the pH range of blood and serum. Therefore, CaS has potential to be applied to sensing Ca2+ ions in extracellular environments. Chapter VI discusses potential future work of KS2 and CaS, following the results achieved in this dissertation. Based on the desirable performances of both sensors in sensing their respective ions, future work could largely be focused on their applications in cellular imaging.

Heart failure is a common condition during which the pumping action of the heart is affected because the heart does not contract or relax properly. Heart failure affects about 5 million Americans, with 550,000 new cases diagnosed each year. Cardiac resynchronization therapy (CRT) is used to treat symptoms and other complications associated with a heart failure. While performing CRT, Implantation of a pacing lead in the left ventricle of the heart is a very challenging surgical procedure performed with fluoroscopy. The target location is often difficult to reach through the tortuous coronary venous anatomy, which varies greatly among individuals. Placement of the pacing lead is an important research topic because the ideal pacing location for some patients with heart disease may be the site of latest contraction in the left ventricle. The purpose of this project is to develop an algorithm to locate and track points on a lead in a sequence of images. The algorithm will track the motion of the points over time and generate displacement plots over time.

<p>In this thesis, inverse problems related to microwave imaging and microwave component design are investigated. Our contribution in microwave imaging for breast tumor detection can be divided into two parts. In the first part, a vectorial 3D near-field microwave holography is proposed which is an improvement over the existing holography algorithms. In the second part, a simple and fast post-processing algorithm based on the principle of blind de-convolution is proposed for removing the integration effect of the antenna aperture. This allows for the data collected by the antennas to be used in 3D holography reconstruction. The blind deconvolution algorithm is a well-known algorithm in signal processing and our contribution here is its adaptation to microwave data processing.</p> <p>Second, a procedure for accelerating the space-mapping optimization process is presented. By exploiting both fine- and surrogate-model sensitivity information, a good mapping between the two model spaces is efficiently obtained. This results in a significant speed-up over direct gradient-based optimization of the original fine model and enhanced performance compared with other space-mapping approaches. Our approach utilizes commercially available software with adjoint-sensitivity analysis capabilities.</p> / Thesis / Master of Applied Science (MASc)

<p>In this thesis we consider the need to generate efficient solvers for inverse imaging problems in a way that supports both quality and performance in software, as well as flexibility in the underlying mathematical models. Many problem domains involve large data sizes and rates, and changes in mathematical modelling are limited only by researcher ingenuity and driven by the value of the application. We use a problem in Magnetic Resonance Imaging to illustrate this situation, motivate the need for better software tools and test the tools we develop. The problem is the determination of velocity profiles, think blood-flow patterns, using Phase Contrast Angiography. Despite the name, this method is completely noninvasive, not requiring the injection of contrast agents, but it is too time-consuming with present imaging and computing technology.</p> <p>Our approach is to separate the specification, the mathematical model, from the implementation details required for performance, using a custom language. The Domain Specific Language (DSL) provided to scientists allows for a complete abstraction from the highly optimized generated code. The mathematical DSL is converted to an internal representation we refer to as the Coconut Expression Library. Our expression library uses the directed acyclic graphs as an underlying data structure, which lends itself nicely to our automatic simplifications, differentiation and subexpression elimination. We show how parallelization and other optimizations are encoded as rules which are applied automatically rather than schemes that need to be implemented by the programmer in the low-level implementation. Finally, we present results, both in terms of numerical results and computational performance.</p> / Master of Science (MSc)

<p>MR phase images contain essential information about local magnetic susceptibility sources in the brain, creating a new type of contrast in magnetic resonance imaging (MRI). The goal of this thesis is to demonstrate with a model of the brain how accurately the transformation of phase to susceptibility takes place.</p> <p>A 3D brain model uses the Forward process to calculate magnetic field perturbations caused by susceptibility properties of the tissues in the model. Homodyne High Pass (HP) filter and SHARP algorithm are used to process the simulated phase images. Similarly, MR magnitude data are simulated using tissue properties such as T₁, T₂^* relaxation times and spin density.</p> <p>The halo ring around red nucleus in the real phase data is believed to be an indicator of a capsule around red nucleus. Similar effect is seen in the simulated phase images without including the capsule of red nucleus in the model, this comparison explains that the halo effect may just be entirely or a part of the phase behavior around red nucleus. A negative susceptibility in the internal capsule region, seen in both simulated and real susceptibility maps, is discussed as a possible artifact caused by the processing techniques after comparing the simulated susceptibility maps produced from unprocessed and processed phase data. The brain model is used to determine the optimum echo time of the initial gradient echo sequence in order to produce a high quality susceptibility map with reasonably low error and better time efficiency.</p> / Master of Applied Science (MASc)

The application of electrochemical methods for the characterization of colloidal quantum dots (QDs) attracts considerable attention as these methods may allow for monitoring of some crucial parameters, such as energetic levels of conduction and valence bands as well as surface traps and ligands under real conditions of colloidal solution. In the present work we extend the applications of cyclic voltammetry (CV) to in situ monitoring of degradation processes of water-soluble CdTe QDs. This degradation occurs under lowering of pH to the values around 5, i.e. under conditions relevant to bioimaging applications of these QDs, and is accompanied by pronounced changes of their photoluminescence. Observed correlations between characteristic features of CV diagrams and the fluorescence spectra allowed us to propose mechanisms responsible for evolution of the photoluminescence properties as well as degradation pathway of CdTe QDs at low pH.